The need and the value of aqueous film-coatings for dosage forms are well documented. Typical examples of publications in this are listed as follows: G. S. Banker and G. E. Peck, "The New, Water-Based Colloidal Dispersions," Pharmaceutical Technology, 5(4), 55-61 (1981); R. E. Pondell, "From Solvent to Aqueous Coatings," Drug Development and Industrial Pharmacy, 10(2), 191-202 (1984); M. B. Davis, G. E. Peck, and G. S. Banker, "Preparation and Stability of Aqueous-Based Enteric Polymer Dispersions," Drug Development and Industrial Pharmacy, 12(10), 1419-1448 (1986); F. Gumowski, E. Doelker, and R. Gurny, "The Use of a New Redispersible Aqueous Enteric Coating Material," 11(2), 26-32 (1987); and R. K. Chang, C. H. Hsiao, and J. R. Robinson, "A Review of Aqueous Coating Techniques and Preliminary Data on Release from a Theophylline Product," 11(3), 56-68 (1987).
In brief, the major reasons for the current high level of interest in aqueous film-coating systems to replace the traditional solventborne coating systems are the demand of environmental protection, increasing cost of the coating solvents, and the availability of several new products for waterborne pharmaceutical coating applications.
The common methods of eliminating or minimizing organic solvents in a coating process for preparing pharmaceutical dosage forms include the following:
1. The coating system employs a solution of coating polymer in a mixed organic and aqueous solvent system such as hydroxypropyl methylcellulose (HPMC) in ethanol/water. This method only partially eliminates the need for organic solvents. PA0 2. The coating system employs an aqueous solution of water-soluble film-forming polymer. This method is limited to water-soluble polymers such as methylcellulose (MC), hydroxypropyl cellulose (HPC), and HPMC. Another limitation is the need of removing a large amount of water during drying and coating processes. PA0 3. The coating system employs an aqueous solution of alkali salt of an enteric polymer such as sodium or ammonium salt of hydroxypropyl methylcellulose phthalate (HPMCP), polyvinylacetate phthalate (PVAP), or cellulose acetate phthalate (CAP). PA0 U.S. Pat. No. 4,017,647 teaches a method for providing enteric coatings on solid pharmaceutical dosage forms in which enteric coatings are provided on solid dosage forms by coating the dosage forms with an aqueous solution of a polymeric substance having carboxy groups in a water-soluble salt form and bringing thus coated dosage forms into contact with an inorganic acid to convert the polymeric substance into the acid form which is insoluble in water. PA0 U.K. Patent Application GB No. 2,057,876 teaches a method of preparing coated medicament-containing cores of a solid unit dosage form with an enteric coating. The coating was applied (e.g., in a coating pan) onto the medicament cores from an aqueous solution of a water soluble salt of a cellulose partial ester of a dicarboxylic acid, the aqueous solution being free from organic solvent, until an enteric coating around each medicament core has been built up. The salt may be a sodium or ammonium salt of HPMCP or CAP. PA0 4. The coating system employs a true latex of film-forming polymer which is prepared by polymerizing selected monomers from a wide variety of essentially water-insoluble vinyl, acrylic, and diene monomers by an emulsion polymerization process. The polymerization process consists of (1) admixing monomers, initiator, surfactant and/or emulsion stabilizer in water, (2) emulsifying the mixture to form an oil-in-water emulsion with monomers in the internal phase, (3) removing air and oxygen from the emulsion, and (4) inducing polymerization to produce a latex dispersion. The coating system employing a true latex is limited to synthetic polymers with water-emulsifiable monomers and purity of the polymer latices in which the residual monomers or other potentially toxic chemicals used in the polymerization process are usually very difficult to remove. PA0 5. The coating system employs the pseudolatex of a water-insoluble film-forming polymer. Pseudolatex is an aqueous colloidal dispersion of polymer which is, for practicle purposes, indistinguishable from a true latex. However, it is prepared by employing a mechanical method of converting a pre-existing water-insoluble polymer into an aqueous colloidal dispersion. PA0 U.S. Pat. No. 4,177,177 teaches a polymer emulsification process comprising intimately dispersing a liquified water insoluble polymer phase at a certain viscosity in an aqueous liquid medium phase (at a certain ratio, and temperature) containing at least one nonionic, anionic or cationic oil-in-water emulsifying agent at a certain concentration, in the presence of an emulsion stabilizer at a certain concentration selected from the group consisting of those hydrocarbons and hydrocarbyl alcohols, ethers, alcohol esters, amines, halides and carboxylic acid esters which are inert, nonvolatile, water insoluble, liquid and contain a terminal aliphatic hydrocarbyl group of at least about 8 carbon atoms, and mixtures thereof, and subjecting the resulting crude emulsion to the action of comminuting forces sufficient to enable the production of an aqueous emulsion containing polymer particles averaging less than 0.5 micron in size. This patent teaches that the disclosed polymer emulsification process is carried out at a temperature of about 40.degree. to 90.degree. C. PA0 U.S. Pat. No. 4,330,338 teaches a coating composition for pharamaceutical dosages. The dosages use a set of FDA-approved polymers with a long history of pharmaceutical and food use. Pseudolatices containing such polymers are used to produce soluble, enteric, or sustained release coatings when the formulations are applied to dosage forms. Various other ingredients besides the polymers are taught to be required in the coating composition. This patent does not teach any art relating to render pseudolatex dispersions to water redispersible solid products. PA0 U.S. Pat. No. 4,462,839 teaches a process for making a polymeric powder which is readily dispersible in water to provide a composition useful for forming an enteric coating on pharmaceutical dosage forms, comprising providing a freshly prepared spherical water-insoluble enteric polymer particles, adding to said dispersion a phosphate salt in an amount sufficient to minimize coalescence of particles during spray drying. Another U.S. Pat. No. 4,518,433 issued to McGinley et al., teaches a similar process except adding acetylated monoglyceride to the dispersion before spray drying to produce the water-redispersible powder. PA0 (I) Contacting PA0 (II) emulsifying said organic phase by adding sufficient water to said organic phase while subjecting the resulting mixture to comminuting force to form a water-in-polymer solution emulsion; and adding to said water-in-polymer solution emulsion an additional amount of water effective to result in a phase inversion to form a polymer solution-in-water emulsion, followed by the optional step of: PA0 (III) passing the polymer solution-in-water emulsion through a particle size reduction means such that the water insoluble polymer is in the form of droplets having an average size in the range of about 0.1 to 0.8 .mu.m, preferably about 0.1 to 0.5 .mu.m, followed by the optional step of: PA0 (IV) removing the organic solvent from the polymer solution-in-water emulsion to form an aqueous colloidal dispersion of polymer, and followed by the optional step of: PA0 (V) drying the aqueous colloidal dispersion of polymer to form a water-dispersible powder, wherein, PA0 (I) Contacting PA0 (II) emulsifying said organic phase by adding sufficient water to said organic phase while subjecting the resulting mixture to a comminuting force to form a water-in-polymer solution emulsion; and adding to said water-in-polymer solution emulsion an additional amount of water effective to result in a phase conversion to form a polymer solution-in-water emulsion, wherein, PA0 (III) passing the polymer solution-in-water emulsion through a particle size reduction means such that the water insoluble polymer is in the form of droplets having an average size in the range of about 0.1 to 0.8 .mu.m, preferably about 0.1 to 0.5 .mu.m, followed by the optional step of: PA0 (IV) removing the organic solvent from the polymer solution-in-water emulsion to form an aqueous colloidal dispersion of polymer, and followed by the optional step of: PA0 (V) drying the aqueous colloidal dispersion of polymer to form a water-dispersible powder, wherein, PA0 1. pH-dependent acidic enteric cellulosic polymers: cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), cellulose acetate succinate (CAS), cellulose acetate propionate phthalate (CAPP), and hydroxypropyl methyl cellulose phthalate (HPMCP). PA0 2. Neutral cellulose esters: cellulose acetate (CA), cellulose acetate butyrate (CAB), cellulose acetate propionate (CAP), and ethyl cellulose (EC). PA0 3. pH-dependent basic cellulosic polymers: cellulose derivatives containing functional groups such as cellulose propionate morpholinobutyrate (CPMB), cellulose acetate diethylaminohydroxypropyl ether. Aminocellulose derivatives such as diethylaminomethyl cellulose, 1-piperidyl-ethyl-hydroxyethylcellulose, and benzylamino-ethylhydroxyethylcellulose. Amino acid esters of cellulose or cellulose derivatives such as cellulose acetate diethylaminoacetate. PA0 4. pH-dependent basic polyvinylpyridine and polystyrene derivatives: poly(2-vinylpyridine), poly(4-vinylpyridine), poly(2-vinyl-5-ethylpyridine), and copolymers of these vinyl monomers or blends of these polymers with each other; copolymers of said vinyl monomers with other vinyl compounds such as esters of acrylic and methacrylic acids, acrylonitrile and styrene monomers, particularly, copoly(2-vinylpyridine/styrene) and copoly(2-methyl-5-vinylpyridine/styrene); copolymers containing imidazoline modified styrene such as imidazoline modified copoly(styrene-acrylonitrile), and polystyrenes modified with basic functional groups such as dimethylaminoethyl groups. PA0 5. Maleic anhydride copolymers: poly(methyl vinyl ether/maleic anhydride), ethylene maleic anhydride, styrene maleic anhydride, and various straight chain and branched C.sub.1 -C.sub.6 alkyl esters of maleic anhydride copolymers. PA0 6. Acrylic/acrylate copolymers and acrylic esters: ethylacrylate/methyl methacrylate copolymers of various monomers ratios (commercially available as Eudragit E-30D and Eudragit L-30D). PA0 7. Other polymers may include biodegradable polymers such as copolymers of lactic and glycolic acids and polypeptides and other polymers such as polyesters, e.g., poly(ethylene terephthalate) which meet the above-defined definition for the water insoluble polymers. PA0 It is contemplated that any mixture or combination of water insoluble polymers can be used in the present invention. PA0 All of the above-described polymers useful in the present invention are known in the art and can be made by known techniques and/or are commercially available. PA0 (A) about 45.5 to about 98 weight %, preferably about 75 to about 90 weight %, of at least one water insoluble polymer, PA0 (B) about 0.5 to about 30 weight %, preferably about 5 to about 15 weight %, of at least one oil-in-water emulsifier which is polymeric, water soluble or water dispersible and nonionic, (C) about 1 to about 27.5 weight %, preferably about 2 to about 10 weight %, of at least one water-in-oil emulsifier which is water insoluble; anionic or amphoteric; more hydrophobic than said oil-in-water emulsifier, PA0 (A) dispersing the powdered, polymeric composition of the present invention in an aqueous solution which comprises at least about 85 weight % water to prepare a coating dope, and PA0 (B) coating a solid medicament core with the coating dope of step (A).